In the nature there are many optically active aminoacids known for their pharmacological properties. It is known that the natural synthesis of these aminoacids brings to aminoacids of L configuration which are endowed of pharmacological activity in man. The (-)-3,4-dihydroxyphenyl-L-alanine, also known as 3-hydroxy-L-tyrosine or as L-(-)-2-amino-3-(3,4-hydroxyphenyl) propanoic acid, which is present in nature in some leguminous plants and which is internationally known as a drug useful in the therapy of the Parkinson's disease under the name of levodopa, has a great importance.
As the chiral syntheses which usually take place in nature are at present difficult to carry out in the field of the chemical synthesis, it is necessary to find methods for the optical resolution of the racemic mixtures of aminoacids or of precursors thereof. A method used for the optical resolution is based on the different chemical-physical properties of diastereoisomer derivatives of the aminoacids themselves, for instance their salts, esters or amides, with an optically active compound.
The different solubility of the two diastereoisomers often makes possible to separate them, under appropriate conditions, by means of a fractionated crystallization.
Harada and Hayakawa Bull. Chem. Soc. Japan, 37, 191, (1964), separated the hydrochlorides of diastereoisomer menthyl esters of some aminoacids by starting the crystallization of a supersaturated solution by means of a diastereoisomer, while Halpern and Westley, Chem. Comm., 421, (1965), similarly separated the paratoluensulfonates of diastereoisomer menthyl esters of aminoacids.
The optical resolution of racemic mixtures of phenylalanine and of phenylglycine is exemplified in U.S. Pat. No. 4,379,941 where it is also named the optical resolution of other aminoacids like 4-hydroxyphenylglycine, 3,4-dihydroxyphenylalanine, tyrosine and tryptophane by means of chromatographic separation on silica gel of diastereoisomer esters coming from the esterification of racemic mixtures of these aminoacids with l-menthol.
All these methods are characterized in that the maximum recovery of product in the optical separation can theoretically reach the 50% of the racemic mixture of the diastereoisomers and, moreover, the process described in U.S. Pat. No. 4,379,941 clearly appears to be a speculative laboratory method without any possibility of an useful industrial exploitation.
The process described in the present invention, on the contrary, is characterized from the very important fact that in theory the whole racemic aminoacid can be transformed into the desired diastereoisomer. Moreover this process is easy to carry out and can be industrially exploited and therefore it is a remarkable progress over the prior art.